Extracellular signal-regulated kinases 1 and 2 phosphorylated neurons in the tele- and diencephalon of rat after visceral pain stimulation: an immunocytochemical study

Gioia, Magda; Galbiati, Sara; Rigamonti, L; Moscheni, Claudia; Gagliano, Nicoletta

doi:10.1016/s0304-3940(01)02008-0

Cited by 24 publications

(16 citation statements)

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“…Since fear and anxiety are modulated by pain and the analgesia network modulates autonomic regulation, ERK activation might also occur in neurons involved to a similar extent in various autonomic activities accompanying pain transmission and modulation (Benarroch, 2001;Gauriau and Bernard, 2002); this would agree with other evidence (Huang et al, 2000;Gioia et al, 2001Gioia et al, , 2003 of an interaction between ERK activation and stress or autonomic activities associated with nociception.…”

Section: Discussionsupporting

confidence: 55%

“…ERK activation has been reported in neurons after noxious stimulation (Gutstein et al, 1997;Huang et al, 2000;Gioia et al, 2001Gioia et al, , 2003 Dai et al, 2002;Galan et al, 2002;Ji et al, 2002). Although ERK activation in rat PAG neurons after pain stimulation has been described (Gioia et al, 2003), no details are available on the location of these activated neurons in relation to the PAG columnar organization.…”

Section: Introductionmentioning

confidence: 99%

“…In neurons, ERK1 and -2 can be activated by various stimuli such as neurotrophic factors, N-methyl-D-aspartate (NMDA), and electrical stimulation. They are involved in neuronal differentiation, signaling, and survival, and in physiological brain processes underlying memory and learning (Lewis et al, 1998;Sweatt, 2001).ERK activation has been reported in neurons after noxious stimulation (Gutstein et al, 1997;Huang et al, 2000;Gioia et al, 2001Gioia et al, , 2003 Dai et al, 2002;Galan et al, 2002;Ji et al, 2002). Although ERK activation in rat PAG neurons after pain stimulation has been described (Gioia et al, 2003), no details are available on the location of these activated neurons in relation to the PAG columnar organization.…”

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Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

2005

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The periaqueductal gray matter (PAG), the midbrain region made up of neuronal columns encircling the cerebral aqueduct, plays a key role in nociception. As the extracellular signal-regulated kinases (ERKs) 1 and 2 are activated after noxious stimulation, we analyzed the distribution of ERKactivated neurons in the PAG after visceral noxious stimulation. Ether-and urethane-anesthetized rats received an intraperitoneal injection of acetic acid or were left untreated and were perfused after 2 hr. Serial sections immunoreacted with an antibody selective for the activated ERKs. Significant ERK activation occurred only in the ether-anesthetized noxious stimulated rats. In these rats, we evaluated the number of ERK-activated neurons and their density as the ratio of the number of immunolabeled neurons to the extension of the region where they were located. ERK-activated neurons were more numerous in the lateral (LPAG) and ventrolateral (VLPAG) columns, but without significant differences. No ERK activation was seen in neurons of the most rostral PAG. The ERK-activated neurons were significantly denser at the intermediate level of the PAG. At the caudal level, they were denser in the LPAG and VLPAG columns, and in the DPAG column at the intermediate and rostral level. These findings suggest that noxious stimulation activates ERKs in neurons involved in the different functional activities related to nociception, overlapping in the PAG columns, and strengthens the role of PAG in integration. © 2005 Wiley-Liss, Inc.Key words: periaqueductal gray matter; nociception; extracellular signal-regulated kinases 1 and 2; immunohistochemistry; ratThe periaqueductal gray matter (PAG) is the midbrain region made up of neurons surrounding the cerebral aqueduct. It is involved in various important functional activities such as fear, anxiety, defensive reactions, and autonomic regulation. Its key role, however, is in pain processing (Bandler and Shipley, 1994; Behbehani, 1995;Westlund, 2000). The PAG is involved in the transmission and modulation of pain, acting on nociceptive ascending and descending systems through complex neural intrinsic circuits (Behbehani, 1995).Anatomical and functional data suggest that the PAG is made up of columns of neurons with different location from the aqueduct, extending for different distances along the cerebral aqueduct axis (Bandler and Shipley, 1994 dorsal (DPAG) column is involved in fear and anxiety processing (Behbehani, 1995), and the lateral (LPAG) and ventrolateral (VLPAG) columns play specific roles in coordinating different strategies for coping with distinct patterns of stress, threat, and noxious stimuli (Bandler and Shipley, 1994).Within the central nervous system, many extracellular stimuli, including noxious stimulation, are converted into specific cellular responses, activating signal-transduction systems such as the mitogen-activated protein kinase (MAPK) cascade, which in turn coordinates cellular activities such as gene transcription, protein synthesis, cell cycle machinery, ...

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

2005

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“…Retrograde tracing studies in rat (Peschanski and Besson, 1984;Chen and Su, 1990;Otake et al, 1995;Novak et al, 2000;Krout et al, 2002) show that PVA receives projections from regions that are important in generating pain perception such as ACC, CeA, parabrachial area (PB), PAG, dorsal and medial raphe nucleus, and nucleus raphe magnus (Price, 2000;Millan, 2002). Although PVA is not commonly known as the pain matrix in the brain, increased c-Fos expression and pERK staining in PVA have been reported in several pain models in rat and mouse (Bullitt, 1990;Davies et al, 1997;Gioia et al, 2001;Chung et al, 2007;Nishii et al, 2008;Zhang et al, 2009). In the present study, pharmacological inactivation of ERK in PVA blocked the acid-induced chronic hyperalgesia in WT mice.…”

Section: Discussionmentioning

confidence: 99%

Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Chen

Liu²,

Chang³

et al. 2010

J. Neurosci.

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Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca 2ϩ channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic musculoskeletal pain is still unclear. Here, we show that acid-induced chronic mechanical hyperalgesia develops in Ca v 3.1-deficient and wild-type but not in Ca v 3.2-deficient male and female mice. We also show that T-channels are required for the initiation, but not maintenance, of acid-induced chronic muscle pain. Blocking T-channels using ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when administered intraperitoneally or intracerebroventricularly, but not intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca v 3.2 T-channeldependent activation of ERK (extracellular signal-regulated kinase) in the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK activation abolished the chronic mechanical hyperalgesia. Our findings suggest that Ca v 3.2 T-channel-dependent activation of ERK in PVA is required for the development of acid-induced chronic mechanical hyperalgesia.

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“…Noxious visceral stimuli by intraperitoneal (i.p.) injection of acetic acid, intracolonic instillation of capsaicin or mustard oil, and noxious colorectal distension (CRD) could evoke ERK activation in the lumbosacral dorsal horn and several cerebral structures involving paraventricular nucleus, hypothalamic anterior, amygdala, and brain stem nuclei, which are involved in pain transmission (Gioia et al 2001;Million et al 2006;Gioia et al 2003;Galan et al 2003). Furthermore, ERK activation in the primary afferent neurons and spinal cord has been suggested to be associated with the development and maintenance of hyperalgesia (Kawasaki et al 2004;Daulhac et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

Zhang

Chung

et al. 2008

J Mol Neurosci

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The activation of extracellular signal-regulated protein kinase (ERK) is essential for pain sensation and development of hyperalgesia in chronic pathological pain. Neonatal maternal separation (NMS) could trigger behavioral hyperalgesia and upregulate central neuronal activity in rats. The present study aims to investigate whether ERK associates with the colorectal distension (CRD)-evoked neuronal response and the upregulated central sensitivity to CRD in NMS rats. Male Sprague-Dawley rat pups were either subjected to NMS or not handled (NH) from postnatal day 2 to day 14. The protein expression of phospho-ERK (p-ERK) and c-fos at the spinal and supraspinal levels of adult rats were quantified and their correlation was analyzed. Western blot analysis revealed significant NMS effect on p-ERK expression in the lumbosacral dorsal horn and thalamus. Immunohistochemistry analysis demonstrated that CRD elevated p-ERK and c-fos expression in the dorsal root ganglia (DRG), laminae I-II of the lumbosacral dorsal horn, thalamic nucleus central medial (CM), paraventricular thalamic nucleus (PV), and anterior cingulate cortex (ACC). Significant NMS effect on p-ERK and c-fos expression was observed in the DRG, and laminae I-II, III-IV, and X of the lumbosacral dorsal horn. Furthermore, a significant interactive effect of NMS and CRD on p-ERK expression was observed in laminae III-IV of the lumbosacral dorsal horn. Correlation analysis revealed the positive association between c-fos- and p-ERK-immunoreactive nuclei numbers in the DRG, lumbosacral dorsal horn, and ACC. These results demonstrate that ERK is actively involved in CRD-evoked neuronal activation in both NH and NMS rats. Moreover, ERK is associated with the upregulated central neuronal sensitivity to noxious CRD in NMS rats, which may be responsible for the behavioral hyperalgesia in NMS rat.

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Extracellular signal-regulated kinases 1 and 2 phosphorylated neurons in the tele- and diencephalon of rat after visceral pain stimulation: an immunocytochemical study

Cited by 24 publications

References 14 publications

Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

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Extracellular signal-regulated kinases 1 and 2 phosphorylated neurons in the tele- and diencephalon of rat after visceral pain stimulation: an immunocytochemical study

Cited by 24 publications

References 14 publications

Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

Cav3.2 T-Type Ca2+Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

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Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain